Trends in Risk Reduction Practices for the Prevention of Lymphedema in the first 12 months after Breast Cancer Surgery

Hi, all,

I've uploaded an article to the File section that was written by a surgeon atMayo in FL. She is asserting that LE risk information, since it has not beenadequately confirmed by research, should not be offered to cancer patientsbecause it creates anxiety for them. She would like surgeons to say less aboutthe risks and about any risk-reduction behaviors, because she believes these layan added burden on patients who may or may not ever develop LE.

For those of us who were never warned about the possibility of LE, or were toldwe didn't need to worry about it because we "couldn't" get it with a sentinelnode biopsy (or because we were "too thin", or because "none of my patients everget LE" or whatever) this is NOT good news or good science. We were never giventhe option of taking early action, because our risk was denied or ignored,perhaps in an effort to "save" us from worry.

As Advocates for Lymphedema here, I just wanted to urge all of you, secondaryand primary alike, to read the article and, if you find it as alarming as I do,to write to the journal editors and/or to the author. Their contact informationis below:

RESULTS: At 6 months, lymphedema was similar between ALND and SLNB patients (p ¼ 0.22), butwas higher in ALND women at 12 months (19% vs 3%, p ¼ 0.005). A clear relationshipexists between relative change in upper extremity volume at 6 and 12 months (Kendall taucoefficient 0.504, p < 0.001). Among the women with 0 to 9% volume change at 6 months,22% had progressive swelling, and 18% resolved their volume changes at 12 months. Overall,75% of ALND and 50% of SLNB patients had persistent worry about lymphedema atfollow-up, and no difference existed in the number of risk reducing behaviors practicedamong the 2 groups (p > 0.34).

CONCLUSIONS: Upper extremity volumes fluctuate, and there is a period of latency before development oflymphedema. Despite the low risk of lymphedema after SLNB, most women worry aboutlymphedema and practice risk reducing behaviors. Additional study into early upperextremity volume changes is warranted to allay the fears of most women and better predictwhich women will progress to lymphedema. (J Am Coll Surg 2013;216:380e389.! 2013 by the American College of Surgeons)

Lymphedema is feared complication after axillary surgeryfor breast cancer. The true incidence of lymphedema isdifficult to determine because it may take years to develop.However, 90% of women who will develop lymphedemado so within 3 years of breast cancer treatment.1,2 Althoughsome authors have argued a prodromal phase to lymphedemaexists, the current literature lacks data on progressionto lymphedema and assumes subtle increases in armvolume remain stable or progress over time.

Frequently cited lymphedema risk factors include thetype of axillary surgery, infection or injury to the ipsilateralarm after surgery, increased weight or body mass index(BMI), and radiation or adjuvant chemotherapy.3 Yetstudies disagree on which risk factors are significant andthey present contradictory data concerning the influenceof each risk factor on the future development of lymphedema.3 Because risk factors are inconsistent, clinicianseducate all breast cancer survivors on precautionary behaviorsin an effort to reduce patient risk for lymphedema.Common precautionary behaviors supported by theNational Lymphedema Network (NLN) include aggressiveskin care to avoid trauma or injury (avoidance ofneedle punctures, blood draws, or intravenous sticks),avoidance of limb constriction (blood pressure cuff inflation,tight clothing), avoidance of extreme temperatures,and frequent use of compression garments (especially forair travel).4 However, the National Lymphedema Networkacknowledges the paucity of high quality evidence supportingthese practices and admits recommendations arebased on expert opinion and physiologic principles.With this background, we reviewed our prospectivelymaintained axillary surgery database to determine ratesof measured and perceived lymphedema, assess patientuptake of precautionary practices, and evaluate for trendsin these practices over time, according to patient surgeryand treatment. We hypothesized that arm volumechanges are not static and that despite the lack of evidencesupporting precautionary behaviors to avoid lymphedemadevelopment, the majority of women fear lymphedemaand, therefore, will follow risk reduction practices.

METHODS

Patients

Between January 2009 and August 2010, we prospectivelyenrolled 134 women into our registry. Significant traveldistance (3 patients), insurance change (7 patients), deathfrom other causes (1 patient), death from breast cancer(1 patient), and withdraw of consent (2 patients) accountedfor those who did not complete 12-month follow-up. Thefinal study population consisted of 120 women, of whom53 had an axillary node dissection (ALND) and 67 hadsentinel node biopsy (SLNB) with baseline, 6-month,and 12-month follow-up. A single surgeon (SAM) performedall surgical procedures. The prospective registryrecords clinical and pathologic characteristics. All patientsconsented to baseline and follow-up ipsilateral and contralateralupper extremity measurements and completed questionnairesregarding their risk reduction practices. Allpatient weights were obtained using the same office digitalelectronic scale by Scale-Tronix. Mayo Clinic InstitutionalReview Board approved this study.

Education, patient interview, and measurements

At our institution, all patients with a new diagnosis of breastcancer complete an intake process by a breast medicinephysician, which includes review of a PowerPoint presentationand a printed Mayo Clinic breast handbook. Thesediscuss diagnosis, treatment (surgery and adjuvant therapies),complications, and issues of survivorship includinglymphedema. As part of this handbook, postoperativerange-of-motion arm exercises and lymphedema identificationpractices are reviewed and demonstrated with allpatients. Patients then proceed to the breast surgery clinicon a subsequent day. Once roomed, patients completea Disability Arm Shoulder Hand (DASH) and FunctionalAssessment Cancer Treatment-Breast (FACT-B) questionnairebefore the consultation. A single surgeon (SAM) theninterviewed all patients, reviewed lymphedema risk,concerns, prevention, and activity before and after surgery.Measurements were then obtained preoperatively with thesame nonelastic tape measure.

Two clinicians (SAM and TG) performed all armmeasurements to limit inter-rater variability at 4-cmincrements, from the nail bed base of the middle fingerto the axillary fold using the same nonelastic tapemeasure. To limit intra-rater variability, measurementsdiffering by more than 1 cm from the contralateral armwere repeated twice to verify the difference, and theaverage of these measures was used to calculate thevolume of a frustrum.

Either SAM or TG saw all patients postoperatively at1 month, 6 months, and 12 months. At these postoperativevisits, patients first completed the Disability ArmShoulder Hand and the Functional Assessment CancerTreatment-Breast questionnaires, a modified version ofthe Lymphedema and Breast Cancer Questionnaire,5and a standardized questionnaire asking about the practiceof precautionary behaviors to reduce the risk of lymphedema,and to assess individual fear and worry about lymphedemarisk. The clinician then specifically asked if thepatient had any current swelling in the operated armand then obtained the arm measurements. We comparedfollow-up and baseline measures for each side andcompared the differences between the ipsilateral andcontralateral arms according to the following formula:

where LE is lymphedema, F is frustrum, vol is volume,f/u is follow-up, and B is baseline. Lymphedema wasdefined as a ratios greater than or equal to 1.10 (10%increase in the ipsilateral arm when compared with thechanges in the contralateral arm).

All patients were then re-educated on the risk of lymphedema;patients deemed to be at highest risk, especiallythose having ALND or axillary radiation, or any symptomaticpatients (perceived but not measured lymphedema),those with volume changes >5%, or those with range-ofmotiondifficulties, were referred for evaluation by a singlelymphedema specialty trained physical therapist. This evaluationconsisted of a 1-time educational visit that includeddiscussion regarding the role of compression sleeves andrange-of-motion exercises. Sleeves were given at patientrequest or if deemed necessary by the physical therapist.No formal decongestive therapy or massage was performedor taught. The physical therapist counseled all patients towear the sleeve if experiencing symptoms but did notrecommend prophylactic use.

At all preoperative and postoperative visits, patientswere counseled (by SAM) to maintain their normalactivity, acknowledge their symptoms, and to return totheir presurgery activity in a gradual fashion. In addition,they were told, in accordance with recently publisheddata, that exercise and weight lifting in a controlledfashion starting with low weight and few repetitionsmay potentially be beneficial in lymphedema prevention6-8 and may offer psychological benefit and improvedrange of motion, without hastening the development oflymphedema.

Data analysis

Patient objective measurements, interview data, and questionnaireresponses were summarized and compared byaxillary surgery group and other patient characteristics.Differences between groups and associations betweenlymphedema, worry, and precautionary behaviors wereassessed using Fisher’s exact test for categorical variablesand the Wilcoxon rank sum test or signed rank test forcontinuous variables. Evaluation was performed usingthe SAS 9.2 operating system and a p value of less than0.05 was considered statistically significant.

RESULTS

Study population characteristics according to surgery typeare listed in Table 1. Women completing SLNB weresimilar in age and BMI to those undergoing ALND,but had smaller tumors and were less likely to receiveadjuvant chemotherapy or radiation. Operations wereperformed on the side ipsilateral to the dominant handin 56 of 120 (47%) and on the side of the nondominanthand in 61 of 120 (51%). All patients completed 6-month and 12-month follow-up.

Overall, 56 of 114 (49%) women with volume changes(progression or regression) had been evaluated by physicaltherapy for the symptoms or because they had an ALND.In all cases, however, garment use was not standardizedand patients were urged to wear compression garmentswhen they had symptoms, but not for prophylactic use.With this method, 7 women progressed to lymphedema(>10% at 12 months), 9 women regressed from 0 to5% at 6 months to <0% by 12 months, and 38 remainedunchanged. The remaining 58 of 114 (51%) did not haveany garment use.

Interview data

More ALND than SLNB patients perceived arm swellingat 6 and 12 months. Interview data identified a similarnumber of ALND patients perceiving swelling at both6 and 12 months (25% vs 31%, p ¼ 0.80) (Table 2).The perception of swelling in SLNB patients was alsosimilar at 6 and 12 months (11% vs 6%, p ¼ 0.76),but was consistently less than that seen in patients havingALND. Interestingly, at all time points and regardless ofthe type of axillary surgery, more patients perceivedswelling than had measured lymphedema. Data fromthe validated instrument paralleled patient perceptions:19% and 25% ALND (p ¼ 0.65) and 5% and 6% ofSLNB patients (p ¼ 1.0) reported an increase in armsize at 6 and 12 months, respectively. Overall, 83% ofpatients had agreement in their measurement and perceptionsof lymphedema; the remaining 17% disagreed with12% perceiving lymphedema without measurement and5% having measured lymphedema without the perception,but this discordance was not statistically significant

Risk factors

At 12 months, we found extent of axillary surgery to bethe only significant risk for developing lymphedema(p ¼ 0.005). Patient age, BMI at baseline and follow-up,type of breast surgery (breast conserving surgery or mastectomy),and receipt of breast or chest wall radiation werenot associated with increased lymphedema (all p > 0.49)(Table 5). Although 11 women reported infection orinjury in the ipsilateral arm 12 months postsurgery, only1 perceived swelling in her arm, and none demonstratedmeasured lymphedema. Finally, patients with measuredlymphedema at 6 and 12 months were more likely tohave had surgery on the side of their nondominant arm:75% and 67%, respectively. Similarly, more patientsperceiving lymphedema also had surgery on the side oftheir nondominant arm: 65% and 60%, respectively.

Overall, patients with lymphedema practiced a similarnumber of precautionary behaviors to those withoutlymphedema.

Patient worry and risk reduction practicesThe majority of patients demonstrated worry about developinglymphedema. At 6 months, 75% of ALND and52% of SLNB patients reported worry about getting lymphedema.Interestingly, patient worry remained consistentat 12 months, with 76% of ALND and 49% of SLNBpatients reporting worry (both p > 0.45) (Table 2). Toreduce future risk of lymphedema, ALND patients practiceda median of 5 risk reducing behaviors at 6 and 12months, and SLNB women followed 4 at both timeperiods (p each > 0.34). Of the 10 precautionary behaviorsassessed, avoidance of IVs, blood pressure cuff inflation,and blood draws were the most commonlypracticed (Table 6). Although at least 96%, 88%, and94% of ALND women practiced these behaviors, respectively,at both time points, fewer, but still the majority,of all SLNB patients followed the same practices (87%,69%, and 76%, respectively). No difference existed inthe frequency of these practices in either group or between6 and 12 months (all p > 0.62). Of the remaining precautionarybehaviors surveyed, ALND women were morelikely to adopt wearing a compression sleeve by 12 monthsthan at 6 (35% vs 15%, respectively, p ¼ 0.003). Otherwise,no difference existed in the adoption or practice ofany precautionary behavior at 12 months when comparedwith 6 months.

DISCUSSION

Breast cancer survivors have long feared lymphedema givenits associated physical and emotional impairments andassociated negative impact on overall quality of life. Toreduce the incidence of lymphedema, surgeons have proactivelytried to limit axillary surgery. The adoption of SLNBas the standard of care for axillary staging attests to thismovement. More recently, practice patterns have demonstrateda decline in ALND after positive SLNB for micrometastaticor isolated tumor cells, suggesting clinicians feelaxillary evaluation is more a diagnostic than a therapeuticprocedure.9 Publication of the American College ofSurgeons Oncology Group (ACOSOG) Z0011 trial nowconfirms the lack of a survival benefit for completionALND in women with 1 or 2 positive nodes completingbreast conserving surgery, adjuvant systemic therapy, andwhole breast radiation.10 In spite of these efforts to minimizeaxillary surgery, the risk of lymphedema remainsbecause there is clearly a small but definite risk of lymphedemaafter SLNB11-15 and a clear but less well documentedrisk of lymphedema after axillary radiation.16The etiology and progression of arm symptoms andmeasurements to lymphedema are unclear. Norman andcolleagues1 demonstrated that women with mild lymphedemaare more prone to progress to severe lymphedema.However, few data document change in arm volumes inthe prodromal or prelymphedema phase that may signalfuture risk for the development of lymphedema. We foundthat although a clear relationship exists between armvolume measurements at 6 months and 12 months, notall patients with an increase in their arm volume from baselineprogress to lymphedema. We demonstrated that 30%(19 of 63 patients) of women with some degree of measurementchange from 0 to 9% at 6 months actually resolvedtheir volume increase by 12 months, with little to nocompression garment usage in the majority of patients. Thisis important because it further demonstrates our inability topredict who will progress to lymphedema and underscoresthe need for baseline ipsilateral and contralateral armmeasurements. In addition, this regression without interventionhighlights the natural fluctuations in arm volumesand underscores the need for consistent long-term, consecutivefollow-up measurements to confirm lymphedema.Importantly and in contrast, those women demonstratinglymphedema at 6 months did not resolve their lymphedemaor decrease their arm measurements at 1 year.Clinicians frequently counsel patients regarding lymphedemarisk based on the presence of previously reportedrisk factors like injury, infection, BMI, age, andsurgery. Lymphedema prediction based solely on thesefactors is unreliable, as evidenced by the multiple studiespresenting conflicting data on each risk factor and on themagnitude of influence each risk factor carries.2,3,17Furthermore, individual recall of these events can besubject to significant bias as demonstrated in our data,10 women reported infection in the arm at 6 monthspostsurgery, but only 5 reported infection since surgeryat 1 year. Clearly, clinician reliance on patient acknowledgementof risk factors may not successfully result inaccurate prediction and stratification of lymphedema risk.Perceived lymphedema remains higher than measuredlymphedema at all time points. Although we founda high degree of concordance between perceptions andmeasurements, we suggest that a perception of lymphedemais more likely to influence the adoption of lymphedemarisk reducing behaviors than is an unrecognizedmeasurement change. This is consistent with the findingsof other investigators, who have demonstrated that symptomaticwomen with lymphedema or those with symptomsor the perception of lymphedema have an overallpoorer quality of life.18-20 Although debate exists on thestandardization of lymphedema evaluation methods,perhaps in reality, from the patient’s perspective it isonly the perception of lymphedema that matters clinicallyand it is this perception that influences quality of lifemore than a measurement change.Just as patients appear to overestimate their long-termrisk of contralateral breast cancer,21 we found that at 12months they also worry in excess of their true risk fordeveloping lymphedema (75% of ALND patients and50% of SLNB patients). Although worry of lymphedemaafter ALND may be more understandable, excess worryafter SLNB may be unfounded, given the sustained lowrisk of developing lymphedema after SLNB. It is possiblethat patient knowledge that lymphedema is unpredictable,devastating, and a permanent complication influencesthe fear and worry of developing lymphedemamany women feel years after surgery. Although theetiology of this worry remains unclear, some suggest itmay be attributed to patient symptoms, treatment regimens,education level, earlier experiences, or even educationand counsel on risk reducing practices.22,23Regardless of its etiology, clinicians must recognize thatpatient worry about the future development of lymphedemais significant. Clinicians struggle in counselingpatients because the development of lymphedema ismultifactorial and the ability to control all risk factorsand patient exposures across studies is merely impossible.Bevilacqua and associates24 developed a nomogram to helppredict development of lymphedema. Internal validationsuggests reasonable concordance when used preoperatively,with a concordance index of 0.706. Although nonomogram can dictate patient care it may help stratifyat risk patients, allowing individualization of riskreduction strategies. Specific implementation strategiesand algorithm development, as opposed to widespreadapplication of all practices, will be critical to determiningthe real value of risk reducing behaviors. Further, thisstrategy will allow early intervention in high risk patientswith physical therapy and intense preventative practices(garments, exercise, and perhaps early decongestivetherapy). Beyond this, it is our opinion that patientswho understand their individual risk and are knowledgeableabout symptoms, arm function, and exercise willultimately incorporate only high yield changes to theirlifestyle. However, this patient understanding can beachieved only with better clinician education.Physicians and allied health staffmust recognize that datasupporting risk reducing behaviors are sparse, and what fewdata are available are contradictory and of poor quality.25-30Despite these flaws, patients adopt these practices vigilantlyand almost uniformly. Furthermore, to our knowledge, ourdata are the first to demonstrate that the practices are adoptedalmost immediately after surgery.This is ironic given thecurrent evidence-based focus on breast cancer care and thelack of proven benefits associated with these practices, butunderstandable given that within 12 months most patientsare just completing adjuvant treatments. Unfortunately,the risk of lymphedema will not be eliminated by simplylimiting axillary surgery. Although practice patterns demonstrateand support a move away from axillary dissection,especially after breast conserving surgery,6 the breast cancercommunity has witnessed an increase in the use of axillaryradiation to help maintain local control. Recent data byCaudle and coworkers31 found axillary radiation tangentsto be adjusted higher in up to 43% of patients in thepost-Z0011 era. Although no debate exists on the importanceof multimodality care, there has been little focus onthe potential side effects from these other treatments

Our study is limited due to small numbers and shortfollow-up. We continue to actively enroll patients in theregistry and are actively following patients annually.Unfortunately, our small numbers make it difficult todetermine the effectiveness of the individual precautionarybehaviors, but the study was not designed to show interventiondifferences, only practice patterns. We opted forcircumferential tape measurements at 4 cm increments,then conversion of the circumferential measurements intovolume calculations as our measurement technique, despiteknowing traditional water displacement is the gold standardfor limb volume assessment. Practical limitations involume displacement prohibited implementation into ourdaily surgical practice. We limited those performing themeasurements to minimize variability in technique andfound this the cheapest and easiest way to standardizeour practice. Consistent circumferential measurementsare an accepted measurement assessment tool for lymphedema.Finally, intervention by physical therapy was notstandardized in patients with volume changes <10%.Although 49% of these women had a formal physicaltherapy evaluation, only 10% had volume changes >5%at 6 months. Garment use was inconsistent but all patientswere encouraged to exercise and use their arm normally.Individualization in surgery and radiation therapiesmay help further minimize the risk of measured orperceived lymphedema. Regardless of risk, however,patients demonstrate worry about developing lymphedema.Unless we can better predict lymphedema, persistingpatient and clinician confusion will reinforce thegeneral application of precautionary behaviors to allbreast cancer survivors without regard to individualpatient risk or documented benefit. Improved risk stratificationof patients and further study into the value of theprecautionary behaviors may help to allay the fears of themajority of SLNB women who are unlikely to everdevelop lymphedema.